Potential Biomarkers of RSV Bronchiolitis Severity Identified

Scientists have identified new biomarkers that appear to predict severity and the risk of wheezing recurrence in children with respiratory syncytial virus (RSV) bronchiolitis.

Writing in the journal Scientific Reports, investigators said expression of the C-X-C motif chemokine ligand (CXCL) 12 was elevated in more severe RSV cases and that patients with higher levels of CXCL13 were more likely to experience recurrence.¹

RSV is a leading cause of acute bronchitis in infants and young children and remains a major cause of global infant mortality despite significant advances in research into RSV, the authors explained.

“During the coronavirus disease 2019 (COVID-19) pandemic, RSV infections declined to low levels due to non-pharmaceutical interventions,” they said, “but in the post-pandemic era, RSV has resurged with altered clinical characteristics.”²

In addition, they said epidemiological evidence suggests that early lower respiratory tract infections in children caused by RSV contribute to the subsequent development of recurrent wheezing and childhood asthma.¹

The investigators said efforts to boost prevention have helped to control RSV, but those interventions have also added significant costs for the health care system.

It is not yet clear what mechanism links RSV to wheezing and asthma, the authors noted. In hopes of filling the existing research gap, the authors sought to identify a reliable universal biomarker for RSV bronchiolitis. They decided to investigate key genes and their RSV-associated signaling pathways.

The investigators enrolled 5 children who were hospitalized with RSV bronchiolitis and 5 age- and sex-matched controls. All of the children were between 1 month and 2 years of age and had RSV-positive nasopharyngeal aspirates. The authors performed blood leukocyte RNA-sequencing to identify hub genes associated with RSV. They then confirmed chemokine expression using flow cytometry. After the initial set of 10 enrollees, the investigators analyzed 50 infants with RSV and 30 controls to see if they experienced recurrent wheezing after 1 year.

Altogether 12 hub genes were identified, with 712 differentially expressed genes, the authors said. The 2 most notable chemokines, the investigators said, were CXCL12 and CXCL13. Heightened expression of CXCL12 was linked with moderate-to-severe cases of RSV bronchiolitis, with an area under the curve (AUC) of 0.835 (95% CI, 0.714-0.956; P < .05). Elevated expression of CXCL13, meanwhile, was linked with recurrent wheezing with an AUC of 0.851 (95% CI, 0.711-0.991; P < 0.05). Specifically, the investigators said CXCL12 levels in excess of 2658.93 pg/ml were a predictor of progression to severe viral pneumonia, and CXCL13 levels above 306.448 pg/ml were associated with subsequent recurrent wheezing.

The findings add to a growing body of research into the role of chemokines in patients’ responses to RSV.

“Studies have shown that chemokines involved in RSV infection can exert chemotactic effects on inflammatory cells and may play a significant role in the pathophysiology of RSV bronchitis,” the authors wrote.

The findings suggest that early monitoring of the 2 chemokines could help facilitate treatment planning by more quickly identifying patients at risk of severe disease and by allowing for closer monitoring of patients at a heightened risk of recurrent wheezing.

Still, the authors said the chemokines are inflammatory markers, and thus they may also vary for reasons other than RSV, such as confounding conditions, individual variation, and lifestyle factors. Therefore, they said further exploration and clinical validation are warranted to better understand when and how to intervene in high-risk cases.

References

1. Zhang L, Lv Y, Du Z, et al. CXCL12 and CXCL13 as potential biomarkers for disease severity and recurrence in respiratory syncytial virus bronchiolitis. Sci Rep. Published online December 8, 2025. doi:10.1038/s41598-025-31062-6

2. Cong B, Koç U, Bandeira T, et al. Changes in the global hospitalisation burden of respiratory syncytial virus in young children during the COVID-19 pandemic: a systematic analysis. Lancet Infect Dis. 2024;24(4):361-374. doi:10.1016/S1473-3099(23)00630-8